Dopamine and norepinephrine are both commonly used to treat shock. This randomized trial compared the effects of dopamine versus norepinephrine in 1679 patients with shock. There was no significant difference in the primary outcome of death at 28 days between the dopamine and norepinephrine groups. However, the dopamine group experienced more arrhythmic events. A subgroup analysis found that dopamine was associated with an increased rate of death in patients with cardiogenic shock specifically, but not in patients with septic or hypovolemic shock. The study concluded that while overall mortality was similar, dopamine use resulted in more adverse events than norepinephrine.

1. Comparison of dopamine
and norepinephrine in the
treatment of shock
Moderator – Dr V.Sachin kumar M.D
Presenter - Dr CH.Santhosh P.G

2. BACKGROUND
Both dopamine and norepinephrine are
recommended as first-line vasopressor agents in
the treatment of shock. There is a continuing
controversy about one agent is superior to the
other.

3. Shock
Shock is the clinical syndrome that results from
inadequate tissue perfusion
Types of shock
 Low stroke volume Vasodilation
 a) Hypovolemic a) Septic
 b) Cardiogenic b)
Anaphylactic
 c) Obstructive c) Neurogenic


4. Cardiogenic Shock
Cardiogenic shock (CS) is characterized by
systemic hypoperfusion due to severe depression
of the cardiac index [<2.2 (L/min)/m2] and
sustained systolic arterial hypotension (<90
mmHg) despite an elevated filling pressure
[pulmonary capillary wedge pressure
(PCWP) >18 mmHg].

5. Pathophysiology of cardiogenic shock

6. Dopamine
Dopamine has varying hemodynamic effects based
on the dose. At low doses(<2mcg/kg/min) it dilates
renovascular bed. At moderate doses(2-
10mcg/kg/min) it has positive chronotropic and
ionotropic effects as a consequence of beta -
adrenergic receptor stimulation. At higher doses ,
vasoconstrictor effect resultsfrom alpha-receptor
stimulation. It is started at an infusion rate of 2-
5mcg/kg/min andthe dose is increased every 2-5
mins to maximum of 20-50mcg/kg/min

7. Adverse effects of dopamine

8. Norepinephrine
Norepinephrine is a potent vasoconstictor and
ionotropic stimulant
It acts on alpha-1,alpha-2,beta-1 but not on beta-
2 receptor.
Dosage -0.5 to 30mcg/min i.v

9. Adverse effects of norepinephrine

10. Study Method
Type of study - randomized trial
Duration - December 19 2003 to October 6th
2007.
Study place - Belgium, Austria , Spain.
Number of patients - 1679

11. Inclusion criteria
1. Age: 18 years or older
2. Mean arterial pressure < 70mm Hg
or Systolic blood pressure < 100mm Hg despite
the fact that adequate amount of fluids(at least
1000ml of crystalloids or 500ml of colloids) had
been administered.
3. Signs of tissue hypo-perfusion like
- altered mental state, mottled skin, urine output
of < 0.5ml/kg/hr or serum lactate level > 2mmol/lt

12. Exclusion criteria
1. Age less than 18 years
2. Who had already received vasopressor
agents(dopamine, noradrenaline,epinephrine
or phenylephrine) for more than 4 hours
during the current episode of shock
3. Had serious arrhythmias such as rapid atrial
fibrillation(>160bpm) or ventricular
tachycardia
4. Declared brain dead

13. Study design
A total of 1679 patients were enrolled- 858 in the
dopamine group and 821 in norepinephrine group
The drug dose was determined according to the
patients body weight
Dose of dopamine could be increased or decreased by
2mcg/kg/min upto maximum of 20mcg/kg/min
Dose of norepinephrine could be increased or
decreased by 0.02mcg/kg/min upto maximum of
0.19mcg/kg/min

14. The patient was still hypotensive after the maximum
dose of drug then open label norepinephrine or
epinephrine or vasopressin was given
Open label dopamine was not allowed any time
Ionotropic agents could be used if needed to increase
cardiac output
When the patients were weaned from vaso- pressor
agents, any open-label norepinephrine that was being
administered was withdrawn first, af- ter which the
trial-drug solution was withdrawn. If hypotension
recurred, the trial-drug solution was resumed first (at
the same maximal dose) and an open-label solution of
norepinephrine was added if needed.

16. Measured variables
1.Vital signs
2.Systolic and diastolic arterial pressures
3.Heart rate
4.Central venous pressure
5.Vardiac output.
6.Arterial and mixed venous blood gas levels
7.Doses of vasoactive agents
8.Respiratory conditions
9.Biologic variables
10.Data on daily fluid balance

17. The above data were recorded
-every 6 hours for 48 hours
-every 8 hours on days 3,4,5
-once a day on days 6,7,14,21 and 28

20. Statistical analysis
Primary end point of the trail was rate of death at 28
days
Secondary end point were rate of death in the icu,in
the hospital,at 6 months and at 12 months,the
duration of stay in the icu and no.of days without
need for organ support (i.e., vasopressors,
ventilators, or renal-replacement therapy);
The time to attainment of hemodynamic stability
(i.e., time to reach a mean arterial pressure of 65
mm Hg)16; the changes in hemodynamic variables

24. Results
. The baseline characteristics of the groups were
similar. There was no significant between-
group difference in the rate of death at 28
days (52.5% in the dopamine group and
48.5% in the norepinephrine group; odds ratio
with dopamine, 1.17; 95% confidence
interval, 0.97 to 1.42; P = 0.10). However,
there were more arrhythmic events among the
patients treated with dopamine than among
those treated with norepinephrine (207 events
[24.1%] vs. 102 events [12.4%], P<0.001)

25. A subgroup analysis showed that dopamine, as
compared with norepinephrine, was associated with
an increased rate of death at 28 days among the 280
patients with cardiogenic shock but not among the
1044 patients with septic shock or the 263 with
hypovolemic shock (P = 0.03 for cardiogenic
shock, P = 0.19 for septic shock, and P = 0.84 for
hypovolemic shock, in Kaplan–Meier analyses).

26. Conclusion
Although there was no significant difference in the
rate of death between patients with shock who were
treated with dopamine as the first-line vasopressor
agent and those who were treated with
norepinephrine, the use of dopamine was associated
with a greater number of adverse events

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